Short-course Radiotherapy Combined With Chemotherapy and Pd-1 Inhibitor for Locally Advanced Colon Cancer(TORCH-C) (TORCH-C)

Short-course Radiotherapy Combined With Chemotherapy and Pd-1 Inhibitor for Locally Advanced Colon Cancer(TORCH-C)

Short-course Radiotherapy Combined With CAPOX and Pd-1 Inhibitor for Locally Advanced Colon Cancer: a Randomized, Prospective, Multicentre, Phase II Trial (TORCH-C)

The study evaluates the combination of immunotherapy of PD-1 antibody and chemotherapy and neoadjuvant short-course radiotherapy in locally advanced colon cancer (LACC). Patients are randomly assigned into two prospective groups: treatment group and observerment group. In treatment group, a total of 60 patients will receive 5*5Gy short-course radiotherapy, followed by 4 cycles of capecitabine plus oxaliplatin (CAPOX) chemotherapy and PD-1 antibody, finally receive the surgery. In observerment group: a total of 60 patients will receive 4 cycles of CAPOX chemotherapy, then receive the surgery. The rate of pathologic complete response （pCR）, long-term prognosis and adverse effects will be analyzed.

This study is a prospective, randomized controlled, multicenter phase II study, with a design of superior efficacy，to compare the efficacy of neoadjuvant short-course radiotherapy combined with CapOX chemotherapy and PD-1 immunotherapy in locally advanced colon cancer. We will consecutively enrolled patients who were diagnosed with locally advanced colon cancer with T4 stage or bulky nodes. A total of 120 patients will be Randomized 1:1 to the treatment group and observerment group. In observerment group, patients will receive 4 cycles of CAPOX (Capecitabine: 1000mg/m2 d1-14 q3w; Oxaliplatin: 130mg/m2 d1 q3w)chemotherapy, then receive the surgery, followed by 4 cycles of CAPOX. In treatment group, patients will receive 5*5Gy short-course radiotherapy, followed by 4 cycles of CAPOXand PD-1 antibody(Serplulimab,300mg d1 q3w), then receive the surgery,followed by 4 cycles of CAPOX.

A total of 60 patients will receive 5*5Gy short-course radiotherapy, followed by 4 cycles of CAPOX chemotherapy and PD-1 antibody, finally receive the surgery.

pCR was defined as the absence, from surgical samples, of malignant cells in the primary site and regional lymph nodes

R0 resection refers to the complete removal of the tumor in the operation with microscopically negative margins

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.

From date of randomization until the date of first documented local-regional failure, assessed up to 3 years

Rate of surgical complications, such as intraoperative hemorrhage, anastomotic leakage, intestinal obstruction, etc.

The surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 5 years from the surgery

Inclusion Criteria: pathological confirmed adenocarcinoma clinical stage T4 and/or bulky nodes the distance from anal verge more than 15 cm without distance metastases age >=18 years old, female and male KPS >=70 without previous anti-cancer therapy or immunotherapy with good compliance signed the inform consent Exclusion Criteria: pregnancy or breast-feeding women history of other malignancies within 5 years serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc. immunodeficiency disease or long-term using of immunosuppressive agents baseline blood and biochemical indicators do not meet the following criteria: neutrophils≥1.5×10^9/L, Hb≥90g/L, PLT≥100×10^9/L, ALT/AST ≤2.5 ULN, Cr≤ 1 ULN allergic to any component of the therapy